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Driver mutations lung cancer

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https://www.readbyqxmd.com/read/29451745/detection-of-ros1-positive-non-small-cell-lung-cancer-on-cytological-specimens-using-immunocytochemistry
#1
Tatjana Vlajnic, Spasenija Savic, Audrey Barascud, Betty Baschiera, Michel Bihl, Bruno Grilli, Michelle Herzog, Julien Rebetez, Lukas Bubendorf
BACKGROUND: Rearrangements of the ROS1 oncogene are found in 1% to 2% of non-small cell lung cancers (NSCLC) and are regarded as mutually exclusive oncogenic driver mutations. Since the approval of targeted therapy for ROS1-positive NSCLC, ROS1 testing has become a part of the diagnostic routine. Fluorescence in situ hybridization (FISH), optionally selected for by immunohistochemistry on histological material, is a common practice for the detection of ROS1 rearrangements. However, NSCLC often is diagnosed by cytology alone, requiring predictive marker testing on cytological specimens...
February 16, 2018: Cancer Cytopathology
https://www.readbyqxmd.com/read/29451020/the-brigatinib-experience-a-new-generation-of-therapy-for-alk-positive-non-small-cell-lung-cancer
#2
Idoroenyi Amanam, Rohan Gupta, Isa Mambetsariev, Ravi Salgia
Lung cancer remains the leading cause of cancer deaths in the world with 1.69 million deaths in 2015. A total of 85% of lung cancer cases are non-small-cell lung cancers (NSCLCs). Driver mutations associated with anaplastic lymphoma kinase (ALK) have been identified in a variety of malignancies, including NSCLC. An ALK inhibitor (crizotinib, ceritinib and alectinib) is the preferred therapeutic approach to those advanced ALK fusion variant-positive NSCLC patients. Brigatinib, a next-generation ALK inhibitor, shows promising activity in ALK-rearranged NSCLC that have previously received crizotinib with response rates in ALTA ranging from 42-50%, intracranial response 42-67% and median progression-free survival 9...
February 16, 2018: Future Oncology
https://www.readbyqxmd.com/read/29434849/family-with-sequence-similarity-83-member-b-is-a-predictor-of-poor-prognosis-and-a-potential-therapeutic-target-for-lung-adenocarcinoma-expressing-wild-type-epidermal-growth-factor-receptor
#3
Takumi Yamaura, Junji Ezaki, Naoyuki Okabe, Hironori Takagi, Yuki Ozaki, Takuya Inoue, Yuzuru Watanabe, Mitsuro Fukuhara, Satoshi Muto, Yuki Matsumura, Takeo Hasegawa, Mika Hoshino, Jun Osugi, Yutaka Shio, Satoshi Waguri, Hirosumi Tamura, Jun-Ichi Imai, Emi Ito, Yuka Yanagisawa, Reiko Honma, Shinya Watanabe, Hiroyuki Suzuki
Lung adenocarcinoma (ADC) patients with tumors that harbor no targetable driver gene mutation, such as epidermal growth factor receptor (EGFR) gene mutations, have unfavorable prognosis, and thus, novel therapeutic targets are required. Family with sequence similarity 83, member B (FAM83B) is a biomarker for squamous cell lung cancer. FAM83B has also recently been shown to serve an important role in the EGFR signaling pathway. In the present study, the molecular and clinical impact of FAM83B in lung ADC was investigated...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29423809/identification-of-driver-mutations-in-rare-cancers-the-role-of-smarca4-in-small-cell-carcinoma-of-the-ovary-hypercalcemic-type-sccoht
#4
Jessica D Lang, William P D Hendricks
Cancer is a complex genetic disease that can arise through the stepwise accumulation of mutations in oncogenes and tumor suppressor genes in a variety of different tissues. While the varied landscapes of mutations driving common cancer types such as lung, breast, and colorectal cancer have been comprehensively charted, the genetic underpinnings of many rare cancers remain poorly defined. Study of rare cancers faces unique methodological challenges, but collaborative enterprises that incorporate next generation sequencing, reach across disciplines (i...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29413968/current-perspective-osimertinib-induced-qt-prolongation-new-drugs-with-new-side-effects-need-careful-patient-monitoring
#5
Mart Schiefer, Lizza E L Hendriks, Trang Dinh, Ulrich Lalji, Anne-Marie C Dingemans
An increasing number of tyrosine kinase inhibitors (TKIs) are available for the treatment of non-small cell lung cancer (NSCLC). QT prolongation is one of the known, but relatively rare, adverse events of several TKIs (e.g. osimertinib, crizotinib, ceritinib). Screening for QT prolongation in (high risk) patients is advised for these TKIs. When a QT prolongation develops, the physician is challenged with the question whether to (permanently) discontinue the TKI. In this perspective, we report on a patient who developed a grade III QT prolongation during osimertinib (a third-generation epidermal growth factor receptor [EGFR]-TKI) treatment...
March 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29413057/tumor-biomarker-testing-in-non-small-cell-lung-cancer-a-decade-of-change
#6
Paul A VanderLaan, Deepa Rangachari, Adnan Majid, Mihir S Parikh, Sidharta P Gangadharan, Michael S Kent, Danielle C McDonald, Mark S Huberman, Susumu S Kobayashi, Daniel B Costa
INTRODUCTION: Although a growing list of essential genomic/immune-based biomarkers are linked to approved non-small-cell lung cancer (NSCLC) therapies worldwide, few reports have detailed the evolution of NSCLC predictive biomarker assessment in routine clinical practice. METHODS: We retrospectively reviewed the first one thousand plus NSCLC patient specimens from our institution analyzed for predictive biomarkers from 2004 to 2017 and evaluated patterns of testing as well as correlation with clinical-pathologic characteristics...
February 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29395567/-immune-checkpoint-inhibitors-antibodies-to-pd1-and-pd-l1-a-new-therapeutic-weapon-against-non-small-cell-bronchial-carcinoma
#7
REVIEW
T Berghmans, B Grigoriu, J P Sculier, A P Meert
INTRODUCTION: Classical therapeutic strategy for advanced and metastatic non-small cell lung cancer, without activable oncogenic driver mutation, has been based mainly on cytotoxic chemotherapy with modest benefits in terms of increased survival. BACKGROUND: A better understanding of the mechanisms involved in the regulation of the immune system led to the development of antibodies directed against immune checkpoints such as PD-L1. The first encouraging clinical data from phase I studies assessing anti-PD1 and anti-PD-L1 antibodies have been confirmed in randomised phase III trials...
January 27, 2018: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/29394493/mouse-models-in-squamous-cell-lung-cancer-impact-for-drug-discovery
#8
Aditi P Singh, Diego Adrianzen Herrera, Yifei Zhang, Roman Perez-Soler, Haiying Cheng
Squamous cell lung cancer (SQCLC) is the second most common subtype of non-small cell lung cancer (NSCLC) and has limited therapeutic options. Its development is likely a result of a multistep process in response to chronic tobacco exposure, involving sequential metaplasia, dysplasia and invasive carcinoma. Its complex genomic landscape has recently been revealed but no driver mutations have been validated that could lead to molecularly targeted therapy as have emerged in lung adenocarcinoma. Few preclinical murine models exist for testing and developing novel therapeutics in SQCLC...
February 2, 2018: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29387480/sequential-her2-blockade-as-effective-therapy-in-chemorefractory-her2-gene-amplified-ras-wild-type-metastatic-colorectal-cancer-learning-from-a-clinical-case
#9
Erika Martinelli, Teresa Troiani, Vincenzo Sforza, Giulia Martini, Claudia Cardone, Pietro Paolo Vitiello, Davide Ciardiello, Anna Maria Rachiglio, Nicola Normanno, Andrea Sartore-Bianchi, Silvia Marsoni, Alberto Bardelli, Salvatore Siena, Fortunato Ciardiello
Background: Constitutive activation of HER2-dependent intracellular signalling by HER2 gene amplification or by HER2 mutations has been demonstrated as a mechanism of primary and secondary cancer resistance to cetuximab or panitumumab in preclinical and clinical models of metastatic colorectal cancer (mCRC). Both HER2 Amplification for Colorectal Cancer Enhanced Stratification (HERACLES) cohort A and My Pathway clinical trials provided clinical evidence that anti-HER2 therapies could be active in these patients...
2018: ESMO Open
https://www.readbyqxmd.com/read/29379323/validation-of-liquid-biopsy-plasma-cell-free-dna-testing-in-clinical-management-of-advanced-non-small-cell-lung-cancer
#10
Vidya H Veldore, Anuradha Choughule, Tejaswi Routhu, Nitin Mandloi, Vanita Noronha, Amit Joshi, Amit Dutt, Ravi Gupta, Ramprasad Vedam, Kumar Prabhash
Plasma cell-free tumor DNA, or circulating tumor DNA (ctDNA), from liquid biopsy is a potential source of tumor genetic material, in the absence of tissue biopsy, for EGFR testing. Our validation study reiterates the clinical utility of ctDNA next generation sequencing (NGS) for EGFR mutation testing in non-small cell lung cancer (NSCLC). A total of 163 NSCLC cases were included in the validation, of which 132 patients had paired tissue biopsy and ctDNA. We chose to validate ctDNA using deep sequencing with custom designed bioinformatics methods that could detect somatic mutations at allele frequencies as low as 0...
2018: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29374051/small-cell-neuroendocrine-tumors-cell-state-trumps-the-oncogenic-driver
#11
Matthew G Oser, Pasi A Janne
Small cell neuroendocrine cancers often originate in the lung, but can also arise in the bladder or prostate. Phenotypically, small cell carcinoma of the bladder (SCCB) shares many similarities with small cell lung cancer (SCLC). It is unknown whether SCCB and SCLC share common genetic driver mutations.
January 26, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29371993/genomic-alterations-of-erbb-receptors-in-cancer-clinical-implications
#12
REVIEW
Rosalin Mishra, Ariella B Hanker, Joan T Garrett
The ERBB family of receptor tyrosine kinases has been implicated in carcinogenesis for over three decades with rigorous attention to EGFR and HER2. ERBB receptors, consisting of EGFR, HER2, HER3, and HER4 are part of a complicated signaling network that activates downstream signaling pathways including PI3K/AKT, Ras/Raf/MAPK, JAK/STAT and PKC. It is well established that EGFR is amplified and/or mutated in gliomas and non-small-cell lung carcinoma while HER2 is amplified and/or over-expressed in breast, gastric, ovarian, non-small cell lung carcinoma, and several other tumor types...
December 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/29351916/pathways-impacted-by-genomic-alterations-in-pulmonary-carcinoid-tumors
#13
Michael K Asiedu, Charles F Thomas, Jie Dong, Sandra C Schulte Tomaszek, Prasidda Khadka, Zhifu Sun, Farhad Kosari, Jin Jen, Julian R Molina, George Vasmatzis, Rui Kuang, Marie Christine Aubry, Ping Yang, Dennis A Wigle
PURPOSE: Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, comprise 30% of all carcinoid malignancies, and are defined histologically as typical carcinoid (TC) and atypical carcinoid (AC) tumors. The role of specific genomic alterations in the pathogenesis of pulmonary carcinoid tumors remains poorly understood. We sought to identify genomic alterations and pathways that are deregulated in these tumors to find novel therapeutic targets for pulmonary carcinoid tumors...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29346604/unique-genetic-profiles-from-cerebrospinal-fluid-cell-free-dna-in-leptomeningeal-metastases-of-egfr-mutant-non-small-cell-lung-cancer-a-new-medium-of-liquid-biopsy
#14
Y S Li, B Y Jiang, J J Yang, X C Zhang, Z Zhang, J Y Ye, W Z Zhong, H Y Tu, H J Chen, Z Wang, C R Xu, B C Wang, H J Du, S Chuai, H Han-Zhang, J Su, Q Zhou, X N Yang, W B Guo, H H Yan, Y H Liu, L X Yan, B Huang, M M Zheng, Y L Wu
Background: Leptomeningeal metastases (LM) are more frequent in non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM. Patients and methods: Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled...
January 15, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29343775/impact-of-concurrent-genomic-alterations-detected-by-comprehensive-genomic-sequencing-on-clinical-outcomes-in-east-asian-patients-with-egfr-mutated-lung-adenocarcinoma
#15
Seijiro Sato, Masayuki Nagahashi, Terumoto Koike, Hiroshi Ichikawa, Yoshifumi Shimada, Satoshi Watanabe, Toshiaki Kikuchi, Kazuki Takada, Ryota Nakanishi, Eiji Oki, Tatsuro Okamoto, Kouhei Akazawa, Stephen Lyle, Yiwei Ling, Kazuaki Takabe, Shujiro Okuda, Toshifumi Wakai, Masanori Tsuchida
Next-generation sequencing (NGS) has enabled comprehensive detection of genomic alterations in lung cancer. Ethnic differences may play a critical role in the efficacy of targeted therapies. The aim of this study was to identify and compare genomic alterations of lung adenocarcinoma between Japanese patients and the Cancer Genome Atlas (TCGA), which majority of patients are from the US. We also aimed to examine prognostic impact of additional genomic alterations in patients harboring EGFR mutations. Genomic alterations were determined in Japanese patients with lung adenocarcinoma (Nā€‰=ā€‰100) using NGS-based sequencing of 415 known cancer genes, and correlated with clinical outcome...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29331646/progress-in-the-management-of-advanced-thoracic-malignancies-in-2017
#16
REVIEW
Roberto Ferrara, Laura Mezquita, Benjamin Besse
The treatment paradigm of non-small cell lung cancer (NSCLC) underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival (OS) both in unselected pretreated patients and in untreated patients with PD-L1 expression ā‰„50%. Furthermore, compelling preliminary results were reported for new combinations of anti-PD-1/PD-L1 agents with chemotherapy or anti-CTLA4 inhibitors. The success of the ICIs appeared to extend to patients with small cell lung cancer (SCLC), mesothelioma or thymic tumors...
January 10, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29325035/amplicon-based-next-generation-sequencing-of-plasma-cell-free-dna-for-detection-of-driver-and-resistance-mutations-in-advanced-non-small-cell-lung-cancer
#17
N Guibert, Y Hu, N Feeney, Y Kuang, V Plagnol, G Jones, K Howarth, J F Beeler, C P Paweletz, G R Oxnard
Background: Genomic analysis of plasma cell-free DNA is transforming lung cancer care, however available assays are limited by cost, turnaround time, and imperfect accuracy. Here we study amplicon-based plasma next-generation sequencing (NGS), rather than hybrid-capture-based plasma NGS, hypothesizing this would allow sensitive detection and monitoring of driver and resistance mutations in advanced non-small cell lung cancer (NSCLC). Methods: Plasma samples from patients with NSCLC and a known targetable genotype (EGFR, ALK/ROS1 and other rare genotypes) were collected while on therapy and analyzed, blinded to tumor genotype...
January 9, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29298799/targeting-her2-aberrations-in-non-small-cell-lung-cancer-with-osimertinib
#18
Shengwu Liu, Shuai Li, Josephine Hai, Xiaoen Wang, Ting Chen, Max M Quinn, Peng Gao, Yanxi Zhang, Hongbin Ji, Darren Cross, Kwok-Kin Wong
PURPOSE: HER2 (or ERBB2) aberrations, including both amplification and mutations, have been classified as oncogenic drivers that contribute to 2-6 percent of lung adenocarcinomas. HER2 amplification is also an important mechanism for acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). However, due to limited preclinical studies and clinical trials, currently there is still no available standard of care for lung cancer patients with HER2 aberrations. To fulfill the clinical need for targeting HER2 in non-small cell lung cancer (NSCLC) patients, we performed a comprehensive pre-clinical study to evaluate the efficacy of a third-generation TKI, osimertinib (AZD9291)...
January 3, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29290998/detection-of-somatic-variants-and-egfr-mutations-in-cell-free-dna-from-non-small-cell-lung-cancer-patients-by-ultra-deep-sequencing-using-the-ion-ampliseq-cancer-hotspot-panel-and-droplet-digital-polymerase-chain-reaction
#19
Jae Sook Sung, Hyon Yong Chong, Nak-Jung Kwon, Hae Mi Kim, Jong Won Lee, Boyeon Kim, Saet Byeol Lee, Chang Won Park, Jung Yoon Choi, Won Jin Chang, Yoon Ji Choi, Sung Yong Lee, Eun Joo Kang, Kyong Hwa Park, Yeul Hong Kim
Highly sensitive genotyping assays can detect mutations in cell-free DNA (cfDNA) from cancer patients, reflecting the biology of each patient's cancer. Because circulating tumor DNA comprises a small, variable fraction of DNA circulating in the blood, sensitive parallel multiplexing tests are required to determine mutation profiles. We prospectively examined the clinical utility of ultra-deep sequencing analysis of cfDNA from 126 non-small cell lung cancer (NSCLC) patients using the Ion AmpliSeq Cancer Hotspot Panel v2 (ICP) and validated these findings with droplet digital polymerase chain reaction (ddPCR)...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290256/uncommon-mutations-in-epidermal-growth-factor-receptor-and-response-to-first-and-second-generation-tyrosine-kinase-inhibitors-a-case-series-and-literature-review
#20
REVIEW
Giulia Galli, Giulia Corrao, Martina Imbimbo, Claudia Proto, Diego Signorelli, Monica Ganzinelli, Nicoletta Zilembo, Milena Vitali, Filippo de Braud, Marina Chiara Garassino, Giuseppe Lo Russo
Epidermal growth factor receptor (EGFR) is the most common driver gene involved in non small cell lung cancer (NSCLC) growth, being found in approximately 10-15% of Caucasian and 40% of Asian patients. A wide variety of pathogenic mutations, deletions, insertions and duplications have been described in EGFR exons 18-21. The presence of the most common among them (e.g. exon 21 L851R and exon 19 deletions) is associated to response to first and second generation EGFR tyrosine kinase inhibitors (TKIs), which have demonstrated clear superiority over chemotherapy in terms of both progression free survival (PFS) and overall survival (OS) in all treatment lines...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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